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Impact of Liposomal Spherical Nucleic Acid Structure on Immunotherapeutic Function
Cassandra E Callmann1, Caroline D Kusmierz1, Jasper W Dittmar1
1Department of Chemistry, International Institute for Nanotechnology, Department of Biomedical Engineering, Northwestern University, Evanston, Illinois 60208, United States.
ACS Central Science
|June 3, 2021
Summary
Liposomal spherical nucleic acids (L-SNAs) offer cancer immunotherapy potential. Modifying liposome composition in L-SNAs optimizes cellular uptake, stability, and anti-tumor efficacy, guiding rational design for novel immunotherapeutics.
Area of Science:
- Nanomedicine
- Immunotherapy
- Materials Science
Background:
- Liposomal spherical nucleic acids (L-SNAs) are promising cancer immunotherapeutics.
- L-SNAs feature a dense arrangement of oligonucleotides around a liposomal core.
- Liposome composition influences L-SNA properties and therapeutic potential.
Purpose of the Study:
- To establish L-SNA design rules by investigating liposome composition effects.
- To correlate lipid tail chain length and saturation with L-SNA biological and immunological activity.
- To optimize L-SNAs for enhanced cancer immunotherapy.
Main Methods:
- Synthesized liposomes with varied lipid tail chain lengths and saturation (DOPC, DMPC, DPPC, DSPC).
- Assessed DNA loading, cellular uptake, serum stability, and immunostimulatory activity.
- Evaluated L-SNA efficacy in 4T1 triple-negative breast cancer (TNBC) and Py8119 models.
Main Results:
- Lipid identity significantly impacts L-SNA DNA loading, uptake, stability, and immune response.
- DPPC-based L-SNAs demonstrated enhanced stability, reduced lung metastases, and delayed tumor growth in TNBC models.
- Encapsulating TNBC cell lysates in DPPC-L-SNAs improved anti-tumor efficacy, especially with oxidized lysates.
Conclusions:
- Liposome composition is a critical factor in modulating L-SNA biological and immunomodulatory properties.
- DPPC-based L-SNAs show superior performance for cancer immunotherapy applications.
- Rational design of L-SNAs by tuning liposome components offers a pathway for developing advanced nanoscale immunotherapeutics.
